课件：chapter 13 antineoplasticdrugs.ppt

卡莫司汀Carmustine N，N’-双（β-氯乙基)-N-亚硝基脲，又名卡氮芥 N, N-bis-(β-chloroethyl)-N-nitrosourea Carmustine is highly lipophilic, easily pass through the blood-brain barrier for the treatment of brain tumors, other central nervous system tumors and malignant lymphoma. Synthesis of Carmustine 13.2 Antimetabolites Interfere with pyrimidine, purine and folic acid for biosynthesis of DNA of tumor cells, so inhibiting metabolism of tumor cell, at last leading to the death of tumor cell. Classification of antimetabolites 1. pyrimidines 2. purines 3. Folic acids 尿嘧啶掺入肿瘤组织的速度较其他嘧啶快，氟的原子半径与氢的原子半径相近，氟化物的体积与原化合物几乎相等，C—F键的稳定性在代谢过程中不易分解。氟尿嘧啶能在分子水平代替正常代谢物，欺骗性地掺入生物大分子，导致“致死合成”。 Fluorouracil can replace normal metabolites at the molecular level, deceptively incorporated of biological macromolecules, resulting in Synthesis of death. 5-氟尿嘧啶，5-fluorouracil, 5-FU 5-氟-2,4（1H, 3H）-嘧啶二酮 5 - fluoro -2,4 (1H, 3H) - pyrimidine-dione 13.2.1 Pyrimidines 本品抗瘤谱比较广，对绒毛膜上皮癌及恶性葡萄胎有显著疗效，对结肠癌、直肠的癌、胃癌等有效，是治疗实体肿瘤的首选药。 Fluorouracil has broad spectrum of anti-tumor, significant effective to choriocarcinoma and malignant mole, effective to colorectal cancer, rectal cancer, stomach cancer, is the first choice for the treatment of solid tumor. Clinical application of Fluorouracil Synthesis of fluorouracil 巯嘌呤 Mercaptopurine 6-Mercaptopurine monohydrate 用于各种急性白血病的治疗，对绒毛膜上皮癌及恶性葡萄胎也有效。 For the treatment of a variety of acute leukemias, also effective to chorionic epithelial cancer and malignant mole. 磺巯嘌呤钠增加了药物的水溶性。遇酸性和巯基化合物均易释放出6-MP，对肿瘤组织有一定的选择性。 Tisupurine is more water-soluble than mercaptopurine (6-MP). Easily release 6-MP under acidic condition or the existing of sulfhydryl compounds, has selectivity to tumor tissue. 磺巯嘌呤钠 Tisupurine Synthesis of tisupurine 盐酸阿糖胞苷 Cytarabine hydrochloride 1-β-D-呋喃型阿拉伯糖胞嘧啶盐酸盐 1-β-D-arabinofuranosyl cytosine hydrochloride 用于治疗急性粒细胞白血病。 Clinical mainly for the treatment of acute myeloid leukemia. Metabolism and stability: 盐酸阿糖胞苷会迅速被肝脏中的胞嘧啶脱氨酶作用脱氨，生成无活性的尿嘧啶阿糖胞苷，故口服吸收较差，通常是通过静脉连续滴